First case of aHUS and Brugada syndrome reported in girl, 15
Both rare diseases linked to sudden severe cardiac outcomes: Report
The first case of a patient with both atypical hemolytic uremic syndrome (aHUS) and Brugada syndrome, an irregular heartbeat disorder that increases the risk of sudden death, was described in a report involving a 15-year-old girl in Oman.
The researchers noted that “atypical HUS is a variable disease that can result in multi-systemic complications if not managed adequately.” In this case, the patient missed two weekly treatments due to travel and also experienced other complications due to these two “very rare disorders that … both have a high predisposition for sudden severe cardiac outcomes,” the team wrote. The patient died within two years of cardiac arrest while sleeping.
“This is the first case reporting a rare outcome of sudden death in a patient with two rare disorders, aHUS and Brugada syndrome,” the researchers wrote.
According to the team, her case highlights that “a prompt diagnosis and proper intervention are of utmost importance to reduce cardiovascular risks and avoid deterioration in [a] patient’s condition.”
The report, “Unusual Presentation of Aggressive Atypical Hemolytic Uremic Syndrome With Brugada Syndrome,” was published in the journal Cureus.
Genetic tests suggest both aHUS and Brugada syndrome type 2
aHUS is caused by the abnormal activation of part of the immune system called the complement cascade. This leads to the formation of blood clots inside small blood vessels that may damage internal organs, particularly the kidneys.
The disease is also characterized by hemolytic anemia, which happens when red blood cells are destroyed faster than they can be made, a condition known as hemolysis. Many patients also have low levels of platelets, the cell fragments that help the blood to clot, and experience acute kidney failure.
Here, researchers from Sultan Qaboos University and two hospitals in Oman described the case of a teenager with aHUS and another rare disease known as Brugada syndrome who died suddenly.
The girl was admitted to the emergency department in July 2022 with fatigue, abdominal pain, nausea, vomiting, loss of appetite, and urine discoloration. Blood tests revealed several abnormalities, including low hemoglobin and platelet levels. Hemoglobin is the protein in red blood cells responsible for transporting oxygen.
The patient was given a blood transfusion. Additional lab tests revealed the presence of red blood cell fragments, or schistocytes, consistent with hemolysis.
Genetic tests showed she had a mutation in the G6PD gene, which encodes the production of an enzyme important for the survival of red blood cells, that’s associated with a form of anemia known as X-linked hemolytic anemia. Additionally, she had a mutation in a complement-associated gene, called CFH, supporting a potential diagnosis of aHUS. She also carried a mutation in the GPD1L gene, suggestive of Brugada syndrome type 2.
On the sixth day of her hospital stay, the girl received plasma exchange therapy, a type of treatment used to replace plasma, which is the liquid portion of blood. However, she developed a severe allergic reaction accompanied by seizures that were thought to be driven by uncontrolled high blood pressure. This was followed by acute kidney failure.
She was given several blood pressure-lowering medications, followed by five plasma exchange sessions, and kidney replacement therapy. She also was given methylprednisolone for three days, followed by oral prednisolone, and later Soliris at 900 mg per week.
After the Soliris treatment, her kidney function and blood parameters started to improve, and the therapy’s dose was increased to 1,200 mg weekly. A genetic test to confirm the diagnosis of aHUS was requested and the plan, while waiting for the results, was to continue treatment with Soliris.
Researchers say case is first to result in patient’s sudden death
Six months after her initial visit, she was again admitted to the hospital with lower abdominal pain, nausea, vomiting, and coughing. Due to traveling, she had missed her regular Soliris dose for two weeks. Lab work revealed signs of acute kidney injury and severe anemia.
She underwent hemodialysis — a type of treatment used to remove waste and excess fluid from the blood when kidney function is compromised — and was given a blood transfusion. Soliris was resumed shortly thereafter, and the patient underwent five plasma exchange sessions.
The patient was discharged home twice, but then twice re-admitted with shortness of breath and other symptoms. Treatment included further blood transfusions and her 14th dose of Soliris. However, her blood parameters worsened and more transfusions were needed.
After once again being discharged home, she continued follow-up appointments for weekly Soliris doses. Her kidney function improved and she stopped having dialysis.
Later blood work, however, revealed abnormalities in several parameters, including low hemoglobin but high platelet and white blood cell counts. After she missed a follow-up consultation, it was found that she had died at home from a sudden cardiac arrest while sleeping, as confirmed by an autopsy.
Noting the patient’s death despite “many hemodialysis and plasma exchange sessions and being put on several treatments,” the researchers stressed the importance of both a prompt diagnosis and treatment adherence in people with aHUS.
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